Extracorporeal membrane oxygenation as a bridging therapy for patients with thiamine deficiency-induced pulmonary arterial hypertension

Thiamine deficiency is characterized by a deficiency of thiamine (vitamin B1), lactic acidosis, pulmonary arterial hypertension (PAH), right-sided heart failure, and peripheral nerve damage. Thiamine deficiency is easily misdiagnosed and missed during clinical practice and is associated with death in severe cases.[1,2] Here we reported a patient who was admitted to the hospital with severe metabolic acidosis and pulmonary hypertension and finally diagnosed with thiamine deficiency by detecting plasma vitamin B1 levels. Since clinically obvious thiamine deficiency is rare, and cases of thiamine deficiency requiring extracorporeal membrane oxygenation (ECMO) treatment are rarer, we believe that our case will be helpful for emergency clinicians.

CASE

A 39-year-old man was admitted to our hospital for half a day with chest tightness due to progressive deterioration caused by weakness for 3 months. One day before admission, he felt chest tightness and shortness of breath. At admission, the patient presented with shock and hypoxemia. Echocardiography showed that the left ventricular ejection fraction (LVEF) was 60%, the right atrial size was 56 mm ×53 mm, the left ventricular size and proportion were within the normal range, and moderate tricuspid regurgitation was observed. The V_max was 3.4 m/s, and the pulmonary arterial pressure was 66 mmHg (1 mmHg=0.133 kPa). The patient experienced cardiac arrest during the treatment and obtained retune of spontaneous circulation (ROSC) with emergency bedside cardiopulmonary resuscitation (CPR) for approximately 2 min. Furthermore, the patient presented with low cardiac output and severe hemodynamic instability, requiring a high dose of noradrenaline (3.33 μg/[kg·min]) to maintain perfusion. The patient was admitted to the intensive care unit for further treatment.

His laboratory tests showed that D-dimer was 14.25 mg/L (reference: 0–0.5 mg/L), accompanied by right heart failure. Pulmonary embolism was considered first. Since his vital signs were unstable for computed tomography pulmonary angiography (CTPA), we gave diagnostic thrombolysis after 50 mg of alteplase thrombolytic therapy. The patient’s symptoms showed no signs of improvement, and even worsened the next day. The main manifestations included a worsening level of consciousness, an ongoing reliance on vasoactive drugs to maintain circulation, liver function damage, hypoxemia, and a sharp increase in D-dimer levels (Table 1).

Table 1.

Laboratory results on the first and second days after admission

The patient was assigned to the right femoral artery and left femoral vein catheterization for venous-artery extracorporeal membrane oxygenation (VA-ECMO), considering that the patient had advanced cardiogenic shock and severe hemodynamic instability. After a successful bypass, the patient’s circulation improved significantly, and the noradrenaline level decreased from 5.55 μg/(kg·min) to 1.3 μg/(kg·min). After the discussion, the patient was diagnosed with a pulmonary embolism that failed to be treated with alteplase. For this reason, we further ordered the pulmonary angiography, and the result indicated no defect in the contrast agent in the bilateral pulmonary arteries, completely ruling out the possibility of pulmonary embolism (Figure 1).

Figure 1.

Pulmonary angiography imaging findings. A: left pulmonary angiography showed no obvious filling defect, suggesting the pulmonary embolism of left pulmonary artery was ruled out; B: right pulmonary angiography showed no obvious filling defect, suggesting the pulmonary embolism of right pulmonary artery was ruled out.

Bedside transesophageal echocardiography ruled out structural heart disease, but the pathogenesis remained unknown. Given the patient’s right heart failure with pulmonary hypertension and lactic acidosis, we tested the plasma vitamin B1 level, which was 0.13 ng/mL (reference: 2–10 ng/mL). We finally diagnosed the thiamine deficiency. Fortunately, after systematic treatments, including supplementation with thiamine 100 mg/d, continuous renal replacement therapy (CRRT), low-dose digoxin, and enteral nutrition, the patient’s hemodynamics gradually improved, and the signs and symptoms of heart failure quickly disappeared. Cardiac function improved significantly in the third stage of ECMO (Figure 2). Pulmonary artery pressure decreased to 43 mmHg, end-diastolic right ventricular size was approximately 27 mm, right atrial size decreased to the normal range, the proportion of atrioventricular was within the normal range, and EF was 65%. ECMO was successfully weaned on day 4, and endotracheal intubation was removed on day 6. He was transferred to the nephrology department for intermittent hemodialysis after 10 d of intensive care unit (ICU) hospitalization because his renal function had not completely recovered, and the patient was finally discharged after 23 d.

Figure 2.

The echocardiography results. A: before treatment, the right heart was enlarged, the end-diastolic diameter of the right ventricle was 34 mm, the size of the right atrium was 56 mm×53 mm, the left heart was compressed, showing a “D” sign, and the pulmonary arterial pressure was 66 mmHg; B: normal echocardiography after treatment with a pulmonary artery pressure of 43 mmHg.

DISCUSSION

Thiamine is an essential water-soluble vitamin that plays an important role in energy metabolism. The main sources of thiamine are grains, vegetables, meat, and nuts. Inadequate thiamine intake may result from an unbalanced diet, such as chronic alcohol abuse, excessive vomiting, starvation, or prolonged consumption of preserved foods.[3] This patient had been eating irregularly in the past six months due to depression and had decreased his intake of thiamine from grains and vegetables. Thiamine deficiency is uncommon in critically ill patients and can be misdiagnosed and missed. Thiamine deficiency is characterized by high cardiac output, small artery vasodilation, and heart failure. Increased pulmonary artery blood flow and capillary pressure are associated with increased left ventricular end-diastolic pressure. Increased pulmonary vascular resistance may be another cause of PAH, resulting in increased cardiac preload and myocardial dysfunction, even leading to heart failure. Accordingly, the main cause of right heart failure is thiamine deficiency syndrome, with normal or increased left heart systolic function.[1-2] Although the diagnostic process may seem fairly straightforward, it is often difficult to establish a diagnosis of thiamine deficiency using routine tests unless vitamin B1 levels are measured.

In our case, the patient developed PAH and right heart failure quickly. Reversible causes should be investigated for the progression and consequences of PHA. However, conventional treatments are often ineffective. VA-ECMO can be a life-saving therapy and a bridge to lung transplantation for idiopathic PAH and long-term chronic PAH.[4,5]

With the improvement of people’s living standards, thiamine deficiency has become rare. Lei et al[6] reviewed 24 literature reports and identified 31 cases of thiamine deficiency caused by chronic alcohol abuse (32.26%), weight loss surgery (sleeve gastrectomy) and gastrointestinal disease (29.03%), mixed factors (16.13%), imprisonment (9.13%), diuretics and other reasons (6.45%). However, thiamine deficiency patients requiring ECMO treatment have been rarely reported in the literature. Shah et al[7] reported that a 33-year-old woman with a severely restricted diet was allergic to corn. The patient presented with progressive shortness of breath and general weakness secondary to chronic malnutrition. Echocardiography revealed significant right ventricular dilation with left ventricular diastolic limitations. During the echocardiography examination, the patient suffered cardiac arrest caused by non-pulsatile electrical activity. Spontaneous circulation was observed after two cycles of CPR. The patient underwent 14 d of VA-ECMO support for cardiovascular instability and severe hypoxemia after cardiac arrest. A diagnosis of thiamine deficiency was established with a serum vitamin B1 level < 2 ng/mL.[8]

Thiamine deficiency is a rare and complicated disease that can be easily missed and misdiagnosed. In patients presenting with life-threatening PAH and circulatory failure, ECMO can be used as a bridge for the recovery of cardiac function. In this case, the patient’s inexplicable PAH, metabolic acidosis, and circulatory failure quickly led to cardiac arrest. Following ECMO support, vitamin B1 levels were obtained, and thiamine deficiency was identified. The pulmonary artery pressure decreased significantly after vitamin B1 supplementation.